This document describes our SPORE renewal application entitled "Novel Targets for Prevention and Therapy of Breast Cancer". This program is based on the premise that molecules involved in the mitogenic, invasive and metastatic behavior of breast cancer are identifiable, and thus can be exploited for improved prognostication, therapy selection, and design of specific biologic therapies for treatment and prevention of disease. In this application a series of interactive research projects are focused on expanding our understanding of the pathogenetic significance of these molecules in breast cancer progression and exploiting this information to develop effective new strategies for breast cancer prevention and treatment. Specific targets chosen for translational research studies include: heparin binding growth factors required for tumor induced angiogenesis (and thus critical for conversion from in situ to invasive breast cancer); metalloprotease secreted by breast cancer cells and their inhibition in preclinical and clinical trials; the exploration of cadmium as an unexpected estrogenic substance potentially involved in breast cancer promotion; the use of graft versus host disease induced by a novel autologous bone marrow transplantation strategy to be tested in preclinical and randomized clinical trials; the development of strategies for breast cancer prevention using newer retinoids; and identification of critical gene products involved in the growth regulation of hormone independent breast cancer and their potential use as prognostic or therapeutic targets. Preclinical and clinical studies of prognostic factors and therapies involving these breast cancer gene products are outlined. Five cores are described including a tumor bank of fresh and frozen breast tumor materials, a repository of breast cancer cell lines, clinical breast cancer research resources, a serum and plasma bank:, and a unique mechanism of research coordination which supports these projects and fosters interaction with other institutional strengths and other SPOREs. A program for continued development of faculty committed to breast cancer research is described with specific examples of young faculty who will benefit from this program as well as examples of recent trainees who have achieved faculty rank and attracted peer-reviewed finding for their work. A portfolio of high priority pilot projects together with a system for prioritization and oversight are discussed which contribute directly to major SPORE projects and translational research activities. Finally, a coherent, tightly structured organization for the SPORE is described which provides accountability, flexibility and optimal interaction within the SPORE, within the institutional structure, and with other SPOREs to achieve the goal of improved outlook for women at risk of breast cancer and for patients already suffering from the disease.